1. Field of the Invention
The present invention relates to a process for producing an optically active halogen-containing alcohol.
2. Description of the Related Art
Optically active halogen-containing alcohols have been produced by an asymmetric synthesis or an optical resolution with a diastereomer. However, it is very difficult to obtain optically active halogen-containing alcohols having a high optical purity and to obtain the alcohols in a large quantity. Thus, few methods have been established as practical ones for producing optically active halogen-containing alcohols.
On the other hand, optical resolution methods using an enzyme have been disclosed in Japanese Unexamined Patent Publication Nos. 2-282,340, 1-233,243, and 1-233,244 all of which have been filed by the present inventors. However, it is still difficult to obtain optically active substances having a high optical purity at a high production yield since the selectivity in the reaction is low. Further, the methods involve several technical problems that the synthesis of the optically active substances in a large quantity at a high reproducibility is difficult since substrates in the reaction are inferior in dispersibility such that the substrates would usually form a heterogeneous system.
As methods for dissolving such problems, attempts have been reported in J. Boutelje et al., Bioorg. Chem., 16, 364 (1988) "A method for the synthesis of cis-N-benzyl-2,5-bismethoxycarbonyl pyridine" and C. H. Wong et al., J. Org. Chem., 53, 1607 (1988) "A method for the synthesis of furylmethyl carbinol" wherein an optical resolution is carried out at a high selectivity by adding an organic solvent in a water system in an asymmetric hydrolysis of an ester with an enzyme.
Further, another attempt has been reported in R. Chenevert et al., Can. J. Chem., 66, 1219 (1988) wherein a buffer solution is used instead of water in order to have a high selectivity in the asymmetric hydrolysis of chlorophenoxy propionate.
However, no report has been published in which such attempts mentioned above were applied for the preparation of a halogen-containing alcohol.
SUMMARY OF THE INVENTION
An object of the present invention is to provide a process for producing an optically active halogen-containing alcohol by an optical resolution through an asymmetric hydrolysis of an alkyl ester of carboxylic acid with an enzyme in an aqueous solution system.
A further object of the present invention is to provide a process for producing an optically active substance having a high optical purity at a high production yield with an excellent reproducibility by adding a specific organic solvent and/or a buffer solution or composition in an aqueous solution system to uniformly disperse a substrate in an optical resolution through asymmetric hydrolysis of a halogenated alkyl ester of a carboxylic acid with an enzyme.
A still further object of the present invention will be apparent to those skilled in the art from the following detailed description and appended claims.
The present invention relates to a process for producing an optically active halogen-containing alcohol represented by the following formula [I] ##STR3## wherein R.sup.1 is a halogen substituted alkyl group, R.sup.2 is selected from the group consisting of a substituted or unsubstituted alkyl group, alkene group, or alkyne group, and a substituted or unsubstituted phenyl group, and C having an asterisk indicates an asymmetric atom,
which process comprises subjecting a halogenated alkyl ester of a carboxylic acid represented by the following formula [II] ##STR4## wherein R.sup.1 and R.sup.2 are the same as mentioned above and R.sup.3 is a group selected from the group consisting of a substituted or unsubstituted alkyl group or alkene group, and a substituted or unsubstituted phenyl group, PA1 to asymmetric hydrolysis with an enzyme in an aqueous solution system.